JIANG, LEI,GUEY, LIN TUNG,MARTINI, PAOLO G.V.,PRESNYAK, VLADIMIR
申请号：
CA3079543
公开号：
CA3079543A1
申请日:
2018.11.21
申请国别(地区):
CA
年份:
2019
代理人:
摘要：
This disclosure relates to mRNA therapy for the treatment of propionic acidemia (PA). mRNAs for use in the invention, when administered in vivo, encode human propionyl-CoA carboxylase alpha (PCCA) and/or human propionyl-CoA carboxylase beta (PCCB), and isoforms thereof, functional fragments thereof, and fusion proteins comprising PCCA and/or PCCB. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of propionyl-CoA carboxylase (PCC) expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of disease-associated toxic metabolites associated with deficient PCCA or PCCB activity, in subjects.
